COVID-19 Science Table Guidance on Antivirals

The summary guidance on all treatment medications for COVID relevant to primary care is in the infographic at the end of this section as well as a detailed section about evidence and important prescribing safety information for Paxlovid. 


  1. Paxlovid can be prescribed by community providers such as physicians and nurse practitioners, as well as by pharmacists. The most common issue with paxlovid is drug interactions, and resources such as the Liverpool covid drug checker, the Ontario Science table guidance.
  2. Patients who are on DOAC’s such as apixaban, rivaroxaban, dabigratran, and edoxaban can use the Ontario Science table guidance for patients on a DOAC and Paxlovid.
  3. Paxlovid is given as 300mg / 100mg PO BID for patients with a GFR > 60, and 150mg/100mg PO BID for those with a GFR between 30-60. While there is no on-label recommendations for those with a GFR < 30, there is recommendations on a dose in this population.

Criteria for Use

WHO (Eligibility): Antiviral (Remdesivir/Paxlovid) are now available for consideration for mildly ill patients who present within 7 days of symptom onset (5 days for Paxlovid) and meet any one of the following eligibility criteria for being in a high-risk population.

Eligibility criteria have changed and as of Dec 9, 2022, the following higher-risk groups are eligible to be tested and assessed for antiviral treatments, such as Paxlovid, in Ontario (Full document from Ontario Health can be found here).

Confirmed COVID-19 diagnosis (based on positive PCR, rapid molecular, or rapid antigen test result), present within 5 days of symptom onset, and meet one or more of the following criteria:

  • >60 years of age
  • 18 years of age or older and immunocompromised
  • 18–59 years of age and at higher risk of severe COVID-19. “higher risk” is defined below:
  1. One or more comorbidity with higher risk of severe COVID-19 disease (detailed list in link) 
  2. Inadequate immunity, i.e.: Unvaccinated or incomplete primary series OR Completed primary series AND last COVID-19 vaccine dose was more than 6 months ago AND last SARS-CoV-2 infection was more than 6 months ago
  3. Social determinants of health may confer an increased risk of disease progression. Individuals who are at a higher risk of poor outcomes from COVID-19 infection based on social determinants of health should be considered priority populations for access to Paxlovid. Individuals at higher risk include Indigenous people, Black people, other members of racialized communities, individuals with intellectual, developmental, or cognitive disability, people who use substances regularly (e.g., alcohol), people who live with mental health conditions, and people who are underhoused.

Combinations of risk factors are associated with higher risk of severe COVID-19.

The “eligible” population is wider than that in the trial population so any likely benefit to the individual patient should be considered in the light of the tip sheets (see helpful tools) and evidence summary below.

Although pregnancy is a risk factor for severe COVID-19, the absolute risk for this population remains low due to the young age and lack of comorbidities of most pregnant individuals. There is no data confirming safety of either Paxlovid or remdesivir in pregnancy. Considerations for the use of specific COVID-19 therapeutics in unvaccinated pregnant women should therefore be made on a case-by-case basis.

Breastfeeding: Warn breastfeeding patients that the effects of Paxlovid on the breastfed infant are not known and they should therefore avoid breastfeeding during and for the 7 days following treatment.

Helpful quick tools

Information updated March 2, 2022  (Note December 10, 2022: There is no substantive new trial evidence since this date. A trial is currently underway in Ontario in the primary care, vaccinated population.)

What is it?

Paxlovid consists of a drug that blocks an enzyme the coronavirus needs to reproduce – a similar mechanism to some anti-HIV drugs – as well as another drug that slows the drug’s breakdown. It has been approved for use in Canada in Jan 2022.

The only data available on the medication is from a single trial in an unvaccinated population (pre-omicron). This RCT among 2,246 high-risk non-hospitalized patients who were unvaccinated was reported to reduce the risk of hospitalization.

Over 28 days 0.7% vs 6.5% were hospitalized in paxlovid vs placebo arms (p<0.0001). This represents an approximate number needed to treat (NNT) of 17 in high-risk unvaccinated patients with COVID delta variant to prevent 1 hospitalization (Deaths were 0% vs 1.3%). NNT 77 for the same subgroup. Laboratory based data suggests an effect is likely to hold for the omicron variant.

The only evidence is for prevention of hospitalisation in high risk patients.

There is no evidence for effect on symptoms or post COVID symptoms. Adverse effects were the same in both arms.

MOST COMMON SIDE EFFECTSOF PAXLOVID: dysgeusia (making everything taste bitter, sour or sweet), diarrhea, hypertension, headache and myalgia.

Pregnant or breastfeeding women, those with active HIV (viral load > 400 copies/ml) or on particular HIV medications, those with liver disease and significant renal impairment and low risk fully vaccinated individuals were excluded from the trial. You can read the trial publication here.

DOSE: 3 tablets (150 mg nirmatrelvir 2 tablets; 100 mg ritonavir 1 tablet) taken together twice daily for 5 days. It is important that all tablets are taken together twice daily. (note there is a dose adjustment for renal impairment which is why the nirmatrelvir comes as 2x150mg)

UNCERTAINTIES: there are no trial results of effectiveness in vaccinated individuals, or with omicron variants. Due to the reduced risk of hospitalization in both of these contexts it is likely that the NNT will be higher where the risk of hospitalization is lower (e.g. vaccinated population and milder variant). For example if the risk of hospitalization is 0.9% the NNT to prevent hospitalization would be 125 (this was the estimated risk of hospitalization in Ontario in the Delta wave in 2021 for the non-Long Term Care population). This NNT will therefore likely be even higher for the Omicron variant.  For this reason treatment is focused on those at higher risk where the potential benefit is clinically significant.

Other important prescribing information

There is quite a long list of contraindications as well as potential serious interactions that require changes in drug dosing or scheduling. The quick interaction checker tools in the “helpful quick tools” section above as well as the product monograph offer good guidance and asking a pharmacist to review where possible as a double check is also recommended.

1. There is a contraindication / dose adjustment for impaired renal function

Contraindicated if GFR <30ml/min; If GFR 30-60 dose adjust to:

150 mg of nirmatrelvir (one tablet rather than two) along with 100 mg of ritonavir, taken together, twice daily, in the morning and evening

2. Paxlovid is not recommended for use in severe hepatic dysfunction

3. There is no data on use in pregnancy and breastfeeding so there is an “only if the risks outweigh the benefits” statement– see full product info sheet for full information.

4. Paxlovid is CONTRAINDICATED with drugs that are highly dependent on CYP3A for clearance. There are also a large number of potentially serious interactions that REQUIRE DOSE CHANGE OR SCHEDULE MODIFICATION. See Table 1 for contraindicated medications and Table 4 for serious interactions requiring modification of therapy or monitoring in the attached tables from the drug datasheet.  Commonly used medications in primary care are flagged in green.  

5.  In addition Paxlovid cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer

Anticancer drugs: apalutamide

Anticonvulsants: carbamazepine, phenobarbital, phenytoin

Antimycobacterials: rifampin

Herbal products: St. John’s Wort (hypericum perforatum)

Health Canada approved Product Monograph including patient medication information

  • When writing a prescription, clearly indicate the following:
    • Confirmed COVID-19
    • Symptomatic for 5 days or less (symptom onset is considered day 0)
    • Increased risk for COVID-19 infection progression [indicate to see above list]
    • eGFR (if known)
    • Send up to date current medication list so pharmacist can do a final interactions check and if appropriate consider adding a note on the prescription “feel free to contact re: drug interactions or concerns”.
    • Include information for pharmacist about decisions on adjustments to other medications
  • Consider renal function and dose adjust accordingly for safety:
    • Normal renal function (eGFR > 60mL/min): 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all three taken together orally twice daily for 5 days
    • Mild-moderate renal impairment (eGFR 30-60 mL/min): 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet), taken together orally twice daily for 5 days.
    • Nirmatrelvir/ritonavir is not recommended for patients with eGFR < 30 mL/min, or severe hepatic impairment (Child-Pugh Class C)
  • Inform patient of the pill burden (6 tablets daily) and emphasize the importance of adherence once initiated to minimize the development of drug resistance.
  • Caution patients to avoid any contraindicated medications used intermittently, e.g. agents for erectile dysfunction, colchicine, loratadine.
  • Advise patients at risk of conceiving to use contraception during and for the 7 days following treatment.
  • Advise patients using oral contraceptives containing ethinylestradiol to use additional contraceptive precautions.
  • Inform the patient of common side effects: dysgeusia (making everything taste bitter, sour or sweet), diarrhea, hypertension, headache and myalgia.
  • Monitor as per usual for clinical illness in high risk patients, and additionally if indicated by potential drug interactions

Where to get Paxlovid (Pharmacies):

Ontario Health have indicated that list of pharmacies that are dispensing Paxlovid will be available at as of Wednesday, April 13 at 8:00 a.m. The list will be regularly updated as the list of participating pharmacies expands.

  • Remdesivir and Nirmatrelvir/Ritonavir (Paxlovid) are antivirals used for the early treatment of COVID-19
  • The benefit of these medications is to prevent hospitalizations amongst high risk patients when given early for symptomatic COVID-19
  • Nirmatrelvir/Ritonavir (Paxlovid) is given orally for 5 days and available through most commercial pharmacies.
  • Remdesivir is given intravenously, as 200mg IV on day one, and 100mg IV on day 2 and 3, and is only available through the HHNB LHIN Home and Community Support Services (HCCSS) via home care as of April 3, 2023
  • Both drugs have equal efficacy in clinical trials, and only a single drug should be given to high risk patients
  • High risk patients include those who are elderly, under vaccinated, immunocompromised, or those with multiple medical conditions
  • Given the health resources needed to give IV remdesivir, the preferred treatment is Nirmatrelvir/Ritonavir (Paxlovid) in high risk individuals
  • Remdesivir should only be considered for those who cannot take Nirmatrelvir/Ritonavir (Paxlovid) are, including those with major drug interactions, those with advanced cirrhosis, or those who cannot take oral medications.
  • Most Nirmatrelvir/Ritonavir (Paxlovid) interactions can be dealt with consulting with pharmacists, as well as using resources such as the Liverpool interaction checker, the Ontario Science table guidance
  • Patients who are on DOAC’s such as apixaban, rivaroxaban, dabigratran, and edoxaban can use the Ontario Science table guidance for patients on a DOAC and Paxlovid
  • Patients with altered renal function can use the Ontario Health guidance for Paxlovid
  • Certain interactions such as antiarrythmics (Amiodarone), anticonvulsants (phenytoin, carbamazepine) should be considered for remdesivir only.
  • Patients who have solid organ transplants should consult with their transplant center due to multiple interactions with paxlovid and anti-rejection medications.
  • Remdesivir should be used with caution in those with severe liver disease.
  • Remdesivir cannot be used in combination with chloroquine/hydroxychloroquine due to reduced drug levels

Remdesivir Request for Home and Community Services

First Dose Intravenous Therapy in the Community Risk Assessment Form

Referral Process to CCC:


I am a physician. How do I refer my patient to the MAB Clinic?

As of March 31, 2023 – St. Joseph’s Healthcare will no longer be offering monoclonal antibodies, paxlovid, or remdesivir to outpatients as part of an organized clinic.  For information on Paxlovid or Remdesivir, please see the resources listed above.

For more information.

Outside Hamilton

Different local pathways will apply. Paxlovid will be accessed through primary care and also referral to your local COVID Care Assessment Centre where remdesivir will also be available for those eligible (see your local CAC for referral forms and process).

COVID-19 antiviral treatment in Ontario